RNAi screening and cancer

RNAi screening and cancer

Various types of cancers are generated through mutations or dysregulations of oncogenes/tumor suppressor genes involved in cell cycles and signaling transduction pathways.

To identify cancer therapeutic targets whose inhibition selectively kills cancer cells, synthetic lethal screening is being developed to identify genes whose intervention suppresses tumor progression only when combined with the dysregulation of the genes.

The recent emergence of genomic technologies, including microarray, RNA interference and chemogenomics, provides platforms to realize this concept.

This research could successfully identify synthetic lethal genes in cancer cells harboring major gene alterations such as p53, RB, K-Ras, or Myc.

Remarkable candidate targets were identified by synthetic lethal screening to find chemosensitizers for paclitaxel and cisplatin. Next, we introduce the chemogenomics approaches that explore chemical compounds that exhibit synthetic lethality to cancer gene alterations. Although the synthetic lethal compounds are of great interest in terms of cancer drug development, a method of identifying target proteins for the phenotypic compounds has been elusive.

The integration of genomic and pharmacological analyses would significantly accelerate the identification of cancer-specific synthetic lethal targets.

References

 Mouse models: Novel in vivo RNAi screen in mice. Lokody I. Nat Rev Cancer. 2013 Sep 13. doi : 10.1038/nrc360 PMID: 24030505